Endothelial cell migration has been shown to be an important early step in the processes of neovascularization and repair of vascular structures. It has been suggested that extracellular matrix components play an important role in epithelial cell adhesion, spreading and migration. Preliminary studies showed a similar requirement for synthesis and secretion of matrix molecules for migration of endothelial cells. Furthermore, the localization and production of matrix components appears to change during the migratory process. Since extracellular matrix provides the substrate on which cells migrate and may influence their cellular processes it seems important to define the subendothelial structures and to determine precisely which matrix components are produced by endothelial cells in situ. We propose to define the structural components present in the subendothelial basement membranes of blood vessels using light and high resolution immunoelectron microscopy, immunochemical and chemical analyses. These findings will be correlated to data obtained in vitro on the properties of endothelial cells in culture from various sources using appropriate chemical, immunochemical and morphological techniques. After establishing the synthesis and secretion of connective tissue macromolecules for the various endothelial cell cultures, changes in matrix components or commpartments (media vs cell layer) will be studied in migrating cells using immunofluorescence, immunoelectron microscopy, immunochemical techniques as well as chemical analysis of biosynthetically-labeled matrix components. In further studies it will be attempted to alter the synthesis, secretion and degradation of the various products and to determine the effects of such alterations on migration. It is felt that these studies will allow us to gain insight into the role a biological substrate has on the important phenomenon of cell migration. Endothelial cell migration is an important process in angiogenesis during tumor growth, during organ development in the repair of wounds, and for maintainence of a continuous non-thrombogenic vascular surface. Our studies will contribute to a better understanding of angiogenesis and equipped with this knowledge, methods of controlling this process in disease states (such as diabetes and atherosclerosis) and repair may be approached.